Drug information leaflets improve parental knowledge of their child's treatment at paediatric emergency department discharge.

BACKGROUND: Hospital discharge is a complex multidisciplinary process that can lead to non-compliance and drugs-related problems. Crucial issue for children is parental knowledge of discharge treatments, especially in the time-limited and stressful environment of an emergency department (ED). OBJECTIVE: To compare parental correct knowledge of treatment with and without supply of customised drug information leaflets for the 10 most commonly prescribed drugs. METHOD: Inclusion criteria: paediatric patients (0-16 years) with French-speaking parents discharged from ED of the paediatric department of Geneva University Hospitals before (phase A) and after (phase B) intervention. INTERVENTION: Supply and brief comment of drug information leaflets focusing on specific information not available in official drugs information documents. Follow-up Semi-structured phone interview within 72 h after discharge to evaluate the percentage of parents with correct knowledge of dose, frequency, duration and indication of drugs. Multivariate analysis to identify factors associated with correct knowledge (phases A/B, drugs collection at usual pharmacy, drugs categories). RESULTS: 125 patients were included (phase A: 56; phase B: 69). Drug information leaflets were given to 63/69 ED patients (91%), covering 96/138 prescribed drugs (70%). Parental knowledge was significantly improved in phase B (dose: 62.3% to 89.1%; frequency: 57.9% to 85.5%; duration: 34.2% to 66.7%; indication: 70.2% to 94.9%; p<0.0001). Phase B and collection of drugs at usual pharmacy were significant factors associated with correct knowledge. CONCLUSIONS: Drug information leaflets significantly improved treatment knowledge of French-speaking parents after paediatric ED discharge. Leaflets are now available online for general population.

Procalcitonin measurement for detection of serious bacterial infection in febrile children: comparison between two automated immunoassays.

OBJECTIVES: To assess the concordance of procalcitonin values at 3 cut-off ranges in a cohort of pediatric samples presenting with fever without source, using two different automated immunoassays. DESIGN AND METHODS: 65 frozen samples from children presenting with fever without source were thawed, tested on both Kryptor and VIDAS systems, and compared using a regression analysis, a Bland-Altman difference plot, and analysis of concordance at the clinically relevant cut-off points. RESULTS: Kryptor and VIDAS PCT results correlated remarkably well (r=0.952), with no significant difference in the frequency distribution over the 3 cut-off ranges (p=0.1384). The strength of the agreement was good (κ=0.759) with an overall concordance of 84.6%. CONCLUSION: Correlation and concordance of PCT values measured by both systems were good. This finding allows clinical implementation of both techniques with the same nominal PCT cut-off values for detection of serious bacterial infection in children presenting with fever without source.

Effect of prolactin on the antigen presenting function of monocyte-derived dendritic cells.

Monocyte derived macrophages (Mphi) and dendritic cells (DC) play critical roles at the interface between innate and adaptive immunity. Both types of cells can effectively phagocytose exogenous antigens, whereas only DC can process and present them efficiently to antigen-specific T lymphocytes. The hormone PRL is also produced by immune cells and is regarded as a key component of the neuroendocrine--immune loop and a local regulator of lymphocyte response. Its main feature is cooperation with cytokines and hemopoietins. Triggering of monocyte PRL receptors with physiological-to-supraphysiological concentrations of PRL up-regulates the GM-CSF receptors, resulting in synergistic PRL-GM-CSF induced maturation of immature (i)DC. Further incubation induces increased antigen-presenting activity at the highest PRL concentrations studied (200 ng/ml). IFN-gamma, release by allogeneic lymphocytes is dependent on T cell-triggered IL-12 release by PRL-preincubated iDC. This, in turn, may be secondary to increased DC expression of CD40 or IFN-gamma. The permissive action of high PRL concentrations in the antigen presenting process may be of significance in initiation of the response against major histocompatibility complex (MHC)-presented self-antigens and may explain the association of hyperprolactinemia with autoimmune diseases.

Ex vivo host response to gastrointestinal cancer cells presented by autologous dendritic cells.

BACKGROUND: Dendritic cells (DCs) capture apoptotic tumors and cross-present their antigens in the MHC class I and class II pathways for recognition by CD4+ and CD8+ T lymphocytes. Here we have tested the ability of fresh surgically resected colon and gastric cancer tumors to specifically activate host T lymphocytes when presented by autologous DCs. METHODS: DCs derived from adherent blood mononuclear cells of five patients, after a 7-day culture with GM-CSF and IL-4, were exposed to apoptotic autologous tumor (AAT) or apoptotic autologous peritumor normal (AAN) cells and cultured 24 h with monocyte-conditioned medium to achieve full DC maturation. Tumor-specific response was evaluated as single-cell cytokine release in an enzyme-linked immunospot (ELISPOT) and as cytotoxicity in a cold target inhibition (51)Cr-release assay. RESULTS: AAT-DCs induced specific IFN-gamma by T lymphocytes of two patients (rectal and gastric cancer), whereas in another two patients (rectal and gastric cancer) this response was depressed with a similar tumor-specific pattern and in one patient (rectal cancer) there was no response. Activation of IFN-gamma release was accompanied by tumor cytotoxicity and both responses were enhanced by IL-12, indicating the functional integrity of patients' lymphocytes. CONCLUSION: These data show that T-cell memory against rectal/gastric carcinoma antigens can be triggered by tumor-loaded autologous DCs. However, escape mechanisms may exist among tumors of the same histological origin that can inhibit this host response. A DC-based antitumor immunological monitoring assay with autologous tumor biopsies may allow patients to be screened to determine those who are suitable candidates for immune-based immunotherapy.

Individual and combined effect of granulocyte-macrophage colony-stimulating factor and prolactin on maturation of dendritic cells from blood monocytes under serum-free conditions.

Prolactin (PRL) shares structural and functional features with haemopoietic factors and cytokine peptides. Dendritic cells (DC) are involved in both initiating the primary and boosting the secondary host immune response and can be differentiated in vitro from precursors under the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) plus other factors. Because PRL has been shown to functionally interact with GM-CSF, we have addressed its role on GM-CSF-driven differentiation of DC. Monocytic DC precursors from peripheral blood mononuclear cells (PBMC) were enriched either by adhesion to a plastic surface or CD14-positive selection and cultured for 7 days in serum-free medium containing GM-CSF, interleukin (IL)-4 and PRL, alone or in combination. Cells with large, veiled cytoplasm, expressing major histocompatibility complex (MHC) class II and the costimulatory molecules CD80, CD86 and CD40 and lacking the monocyte marker CD14, were considered as having the phenotype of cytokine-generated DC. Functional maturation was assessed by proliferation and interferon-gamma (IFN-gamma) release of allogeneic T lymphocytes. Physiological (10-20 ng/ml) concentrations of PRL interacted synergistically with GM-CSF and the effect was similar to that induced by IL-4 on GM-CSF-driven DC maturation. When used alone, the physiological concentrations of PRL were inhibitory, whereas higher concentrations (80 ng/ml) were stimulatory. The synergistic effect of PRL may in part be caused by its ability to counteract the down-modulation of the GM-CSF receptor observed in serum-free conditions. These data provide further evidence of the significance of PRL in the process of T lymphocyte activation.

[Tumor samples as a tool for large-scale monitoring of antigen-specific lymphocytes in gastric and colorectal neoplasms]. / L'utilizzo di campioni di tessuto tumorale come mezzo per il monitoraggio su larga scala dei linfociti antigene specifici nelle neoplasie gastriche e colorettali.

The characterization of tumor-associated antigens has enabled to direct the host immune response towards the autologous tumor through appropriate loading and presentation of the antigen. In vivo conditions that generate large numbers of tumor antigens would be an important step in vaccine strategies. In this study we have therefore tested the ability of freshly isolated gastric and colorectal cancer cells to induce a specific anti-tumor response in autologous T lymphocytes. Because dendritic cells (DC) are critically involved in both initiating and boosting host immune responses, they have been used to present apoptotic bodies generated by irradiated tumor cells. Results show that these native antigens stimulate T cytotoxic response against tumor, but not peritumor normal tissues. Induction of IFN-gamma secreting cell activity, which is a standard readout in current cancer vaccine protocols, was also demonstrated by Elispot single-cells assay. These data show the antigenicity of gastric and colorectal tumor cells and open new perspectives in immunotherapy.

Hepatitis C virus acute exacerbation during chemotherapy and radiotherapy for oesophageal carcinoma.

AIMS: We report the first case of an hepatitis C virus positive patient presenting with a solid tumor and developing an exacerbation of his hepatitis C after chemotherapy. CASE REPORT: A 56-year-old white male, previously infected with hepatitis C virus and treated for epidermoid carcinoma of the oesophagus, developed hepatitis (alamine aminotransferase 2376 U/l and aspartate aminotransferase 2262 U/l) after chemotherapy with cisplatin and vinblastine. METHODS: Polymerase chain reaction detected hepatitis C virus RNA in the serum during the acute phase, which returned to negative 14 weeks later. DISCUSSION: Viral replication was probably increased during immunosuppression induced by chemotherapy. Enhanced cellular immune response in the recovery phase was the most likely cause of the hepatitis. CONCLUSIONS: More attention should be paid to liver function tests in patients with a previous history of hepatitis C virus infection. Polymerase chain reaction identification of hepatitis C virus RNA can be a very useful tool that permits rapid diagnosis and appropriate management of such cases.